[Changes and significance of type 2 innate lymphoid cells and their related factors in bronchopulmonary dysplasia]. / 2åž‹å›ºæœ‰æ·‹å·´ç»†èƒžåŠå ¶ç›¸å ³å› å­åœ¨æ”¯æ°”ç®¡è‚ºå‘è‚²ä¸è‰¯ä¸­çš„å˜åŒ–åŠæ„ä¹‰.

OBJECTIVES: To investigate the changes and significance of type 2 innate lymphoid cells (ILC2), interleukin-33 (IL-33), interleukin-25 (IL-25), thymic stromal lymphopoietin (TSLP), interleukin-5 (IL-5), and interleukin-13 (IL-13) in peripheral blood of preterm infants with bronchopulmonary dysplasia (BPD). METHODS: A total of 76 preterm infants with a gestational age of <32 weeks and a length of hospital stay of ≥14 days who were admitted to the Department of Pediatrics of the Affiliated Hospital of Jiangsu University from September 2020 to December 2021 were enrolled. According to the diagnostic criteria for BPD, they were divided into a BPD group with 30 infants and a non-BPD group with 46 infants. The two groups were compared in terms of the percentage of ILC2 and the levels of IL-33, IL-25, TSLP, IL-5, and IL-13 in peripheral blood on days 1, 7, and 14 after birth. RESULTS: The BPD group had significantly lower birth weight and gestational age than the non-BPD group (P<0.05). On days 7 and 14 after birth, the BPD group had significantly higher levels of ILC2, IL-33, TSLP, and IL-5 than the non-BPD group (P<0.05), and these indices had an area under the curve of >0.7 in predicting the devolpment of BPD (P<0.05). Multivariate logistic regression analysis showed that after adjusting for gestational age and birth weight, peripheral blood IL-33, TSLP and IL-5 on days 7 and 14 after birth were closely related to the devolpment of BPD (P<0.05). CONCLUSIONS: Early innate immune activation and upregulated expression of related factors may be observed in preterm infants with BPD. ILC2, IL-33, TSLP, and IL-5 may be used as biological indicators for early diagnosis of BPD.

Abscisic Acid Inhibits Rice Protein Phosphatase PP45 via H2O2 and Relieves Repression of the Ca2+/CaM-Dependent Protein Kinase DMI3.

In plants, Ca2+/calmodulin-dependent protein kinase (CCaMK) is a positive regulator of abscisic acid (ABA) responses, including root growth, antioxidant defense, and tolerance of both water stress and oxidative stress. However, the underlying molecular mechanisms are poorly understood. Here, we show a direct interaction between DMI3 (Doesn't Make Infections 3), a rice (Oryza sativa) CCaMK and PP45, a type 2C protein phosphatase in rice (PP2C). This interaction involves the CaM binding domain of DMI3 and the PP2C domain of PP45. In the absence of ABA, PP45 directly inactivates DMI3 by dephosphorylating Thr-263 in DMI3. However, in the presence of ABA, ABA-induced H2O2 production by the NADPH oxidases RbohB/E inhibits the activity of PP45 not only by inhibiting the expression of PP45 but also by oxidizing Cys-350 and Cys-428 residues to form PP45 intermolecular dimers. ABA-induced oxidation of Cys-350 and Cys-428 in PP45 blocked the interaction between PP45 and DMI3 and substantially prevented PP45-mediated inhibition in DMI3 activity. Genetic analysis indicated that PP45 is an important negative regulator of ABA signaling. These results reveal important pathways for the inhibition of DMI3 under the basal state and for its ABA-induced activation in rice.

Frequency and correlates of violence against patients with schizophrenia living in rural China.

BACKGROUND: Violence against patients with schizophrenia is very common, however it is rarely studied in China, especially in primary health care institutions of rural areas. Therefore, we investigated the frequency of violence against patients with community-living schizophrenia in rural China and examined its associated factors and impact on quality of life (QoL) and social function. METHOD: A survey was conducted among 487 patients with schizophrenia living in rural communities. Data about violent victimization experiences in the past 6 months, demographic information, and clinical characteristics were collected by questionnaires. RESULTS: We found that 92 (18.9%) of 487 subjects experienced at least one type of violent event in the past 6 months. Logistic regression analysis suggested that a history of conducting dangerous behaviors(OR = 1.702, P = 0.02, 95%CI: 1.05-2.73), higher Brief Psychiatric Rating Scale (anxiety domain) score (OR = 1.15, P = 0.02, 95%CI: 1.01-1.304) and lower hospitalization rates (OR = 0.89, P = 0.04, 95%CI: 0.81-0.99) were significantly associated with violent victimization in patients with schizophrenia. Analysis of covariance showed the victims of violence tended to have worse social function in patients with schizophrenia living in rural communities of China (P = 0.04). CONCLUSIONS: Individuals with schizophrenia living in rural China had a high risk of being exposed to violence and violent victimization of patients with schizophrenia had adverse consequences for social function. More attention is needed for those patients experiencing violent events, because they are simultaneously possible to conduct dangerous behaviors.

Unusual and Highly Bioactive Sesterterpenes Synthesized by Pleurotus ostreatus during Coculture with Trametes robiniophila Murr.

Candida albicans and Cryptococcus neoformans, human-pathogenic fungi found worldwide, are receiving increasing attention due to high morbidity and mortality in immunocompromised patients. In the present work, 110 fungus pairs were constructed by coculturing 16 wood-decaying basidiomycetes, among which coculture of Trametes robiniophila Murr and Pleurotus ostreatus was found to strongly inhibit pathogenic fungi through bioactivity-guided assays. A combination of metabolomics and molecular network analysis revealed that 44 features were either newly synthesized or produced at high levels in this coculture system and that 6 of the features that belonged to a family of novel and unusual linear sesterterpenes contributed to high activity with MICs of 1 to 32 µg/ml against pathogenic fungi. Furthermore, dynamic 13C-labeling analysis revealed an association between induced features and the corresponding fungi. Unusual sesterterpenes were 13C labeled only in P. ostreatus in a time course after stimulation by the coculture, suggesting that these sesterterpenes were synthesized by P. ostreatus instead of T. robiniophila Murr. Sesterterpene compounds 1 to 3 were renamed postrediene A to C. Real-time reverse transcription-quantitative PCR (RT-qPCR) analysis revealed that transcriptional levels of three genes encoding terpene synthase, farnesyl-diphosphate farnesyltransferase, and oxidase were found to be 8.2-fold, 88.7-fold, and 21.6-fold higher, respectively, in the coculture than in the monoculture, indicating that biosynthetic gene cluster 10 was most likely responsible for the synthesis of these sesterterpenes. A putative biosynthetic pathway of postrediene A to postrediene C was then proposed based on structures of sesterterpenes and molecular network analysis.IMPORTANCE A number of gene clusters involved in biosynthesis of secondary metabolites are presumably silent or expressed at low levels under conditions of standard laboratory cultivation, resulting in a large gap between the pool of discovered metabolites and genome capability. This work mimicked naturally occurring competition by construction of an artificial coculture of basidiomycete fungi for the identification of secondary metabolites with novel scaffolds and excellent bioactivity. Unusual linear sesterterpenes of postrediene A to C synthesized by P. ostreatus not only were promising lead drugs against human-pathogenic fungi but also highlighted a distinct pathway for sesterterpene biosynthesis in basidiomycetes. The current work provides an important basis for uncovering novel gene functions involved in sesterterpene synthesis and for gaining insights into the mechanism of silent gene activation in fungal defense.

Sexual dysfunction in Chinese rural patients with schizophrenia.

BACKGROUND: Sexual dysfunction is common in patients with schizophrenia, however it is poorly studied in China, especially in primary health care institutions in rural areas. We investigated the prevalence of sexual dysfunction and its correlates including quality of life (QoL), in schizophrenia patients treated in primary care in a rural area in China. METHOD: By using a random numbers table, 21 small town primary care service centers (from 63 totally) were selected in the study. Data of 720 community-dwelling patients with schizophrenia in rural area with diagnoses according to DSM -IV or ICD-10 were collected by interviews. Data on socio-demographic and clinical characteristics including sexual dysfunction and quality of life (QoL) were collected using a standardized protocol and data collection procedure. Data were analyzed using chi-square tests, t-tests, U-tests, ANCOVA and multiple logistic regression as appropriate by SPSS 21.0.The level of significance was set at 0.05 (two-tailed). RESULTS: In this sample, sexual dysfunction was found in 71.3% of the whole sample, 82.7% of female patients and 64.5% of male patients. Multiple logistic regression analysis showed that older age (OR = 1.06, P<0.001, 95%CI: 1.04-1.09) and higher Brief Psychotic Rating Scale (negative domain) score (OR = 1.16, P = 0.01, 95%CI: 1.02-1.31) were significantly associated with sexual dysfunction. Contrary to previous findings, sexual dysfunction was not associated with quality of life after controlling for confounding variables. CONCLUSIONS: More than 2/3 of schizophrenia patients living in a rural area complained of sexual dysfunction, which was associated with older age and more negative psychotic symptoms. Primary care physicians should pay attention to sexual dysfunction during the assessment and treatment of patients with schizophrenia in rural areas in China.

Oxymatrine Inhibits Influenza A Virus Replication and Inflammation via TLR4, p38 MAPK and NF-κB Pathways.

Oxymatrine (OMT) is a strong immunosuppressive agent that has been used in the clinic for many years. In the present study, by using plaque inhibition, luciferase reporter plasmids, qRT-PCR, western blotting, and ELISA assays, we have investigated the effect and mechanism of OMT on influenza A virus (IAV) replication and IAV-induced inflammation in vitro and in vivo. The results showed that OMT had excellent anti-IAV activity on eight IAV strains in vitro. OMT could significantly decrease the promoter activity of TLR3, TLR4, TLR7, MyD88, and TRAF6 genes, inhibit IAV-induced activations of Akt, ERK1/2, p38 MAPK, and NF-κB pathways, and suppress the expressions of inflammatory cytokines and MMP-2/-9. Activators of TLR4, p38 MAPK and NF-κB pathways could significantly antagonize the anti-IAV activity of OMT in vitro, including IAV replication and IAV-induced cytopathogenic effect (CPE). Furthermore, OMT could reduce the loss of body weight, significantly increase the survival rate of IAV-infected mice, decrease the lung index, pulmonary inflammation and lung viral titter, and improve pulmonary histopathological changes. In conclusion, OMT possesses anti-IAV and anti-inflammatory activities, the mechanism of action may be linked to its ability to inhibit IAV-induced activations of TLR4, p38 MAPK, and NF-κB pathways.

Emodin Inhibition of Influenza A Virus Replication and Influenza Viral Pneumonia via the Nrf2, TLR4, p38/JNK and NF-kappaB Pathways.

Lasting activations of toll-like receptors (TLRs), MAPK and NF-κB pathways can support influenza A virus (IAV) infection and promote pneumonia. In this study, we have investigated the effect and mechanism of action of emodin on IAV infection using qRT-PCR, western blotting, ELISA, Nrf2 luciferase reporter, siRNA and plaque inhibition assays. The results showed that emodin could significantly inhibit IAV (ST169, H1N1) replication, reduce IAV-induced expressions of TLR2/3/4/7, MyD88 and TRAF6, decrease IAV-induced phosphorylations of p38/JNK MAPK and nuclear translocation of NF-κB p65. Emodin also activated the Nrf2 pathway, decreased ROS levels, increased GSH levelss and GSH/GSSG ratio, and upregulated the activities of SOD, GR, CAT and GSH-Px after IAV infection. Suppression of Nrf2 via siRNA markedly blocked the inhibitory effects of emodin on IAV-induced activations of TLR4, p38/JNK, and NF-κB pathways and on IAV-induced production of IL-1ß, IL-6 and expression of IAV M2 protein. Emodin also dramatically increased the survival rate of mice, reduced lung edema, pulmonary viral titer and inflammatory cytokines, and improved lung histopathological changes. In conclusion, emodin can inhibit IAV replication and influenza viral pneumonia, at least in part, by activating Nrf2 signaling and inhibiting IAV-induced activations of the TLR4, p38/JNK MAPK and NF-κB pathways.

The predictors to self-reported and performance-based physical function in knee osteoarthritis patients: a cross-sectional study.

Background: Osteoarthritis (OA) knee patients have limited ability in physical function, or difficulties with physical tasks and activities may develop disability. This study aimed to observe the predictors of self-reported and performance-based physical function in patients with knee OA by analyzing the impacts of demographic, pathological, and muscle impairment factors. Methods: 135 knee OA patients participated in this study to complete self-reported questionnaires using Knee Injury and Osteoarthritis Outcome Score (KOOS). When measuring performance-based physical function, a 6-meter gait speed (6MGS) test was measured to evaluate their mobility, and a 5-time Sit-to-Stand test (5STS) was assessed to evaluate their balance. Pain intensity, knee extensor and flexor muscle strength, age, body mass index (BMI), durations of symptoms, and radiographic severity were also collected. Spearman correlation and stepwise multiple linear regression were used to explore the association and predictors in self-reported and performance-based physical function. Results: BMI and durations of symptoms did not indicate any significant correlation with either self-reported or performance-based physical function. Age is significantly negatively associated with 6MGS (r 2 = -0.383, p < 0.01), while knee extensor muscle strength has a moderate correlation with 5STS (r 2 = -0.528, p < 0.01). In the stepwise multiple linear regression models, pain intensity (ß = 0.712, p < 0.001), knee flexor muscle strength (ß = 0.112, p = 0.042) were significantly associated with self-reported physical function in daily activities and contributed to 55.0% of the variance in KOOS-PF score. Knee muscle strength, including knee extensor (5STS: ß = -0.428, p < 0.001) and flexor muscle strength (6MGS: ß = 0.367, p < 0.001), were the main predictors with performance-based physical function. Conclusion: Pain intensity was the leading risk factor of self-reported physical function, and knee flexor muscle strength contributed as well. The severity of knee OA, durations of symptoms and BMI did not contribute to physical function. However, knee extensor and flexor muscle strength were the main predictors of performance-based performance. Our results show that strengthening of weak knee muscles in both quadriceps and hamstring muscle strength should be considered a priory consideration in knee OA no matter if people are in the early or end-stage of knee OA.

Early immune response of neuronal cells (U87) to heavy metal Cd or Pb exposure.

Heavy metals such as lead (Pb) and cadmium (Cd) exist as particulate matter (PM) in the air and can cause biological damage to cells, animals, and humans. However, the mechanism underlying the toxic effects of heavy metals on nerve cells has not yet been completely identified. Glioma is the most common and fatal tumor in the central nervous system; the U87 human glioblastoma cell line is commonly used when researching brain cancer, including aggressive malignant gliomas. Therefore, in this study, cell viability, cytotoxicity, and interleukin-6 (IL-6) levels were analyzed to confirm the effect of Cd and Pb exposure on U87 cells. On confirming the absence of significant effects on cell viability at low concentrations of heavy metals, Cd and Pb exposure had no effect on lactic acid dehydrogenase (LDH) activity at the concentrations (1 µg/L, 30 µg/L, and 1 mg/L) used in this study, and there was a remarkable effect of Cd and Pb exposure on the inflammatory response of these cells. Our findings provide a basis for future research elucidating the effects of heavy metal exposure on cellular pathology. Systematic studies with higher heavy metal concentrations and precision are warranted to deepen our understanding of the relationship between heavy metal exposure and neuronal responses.

Two-year cohort-up study of clozapine prescription in Chinese patients with schizophrenia treated in rural primary care.

Few studies have examined the clozapine in cohort studies of Chinese patients with schizophrenia in rural primary care. The objective of this two-year cohort study was to describe the usage of clozapine and investigate and identify the demographic, clinical correlations and risk variables which affect the use of clozapine in patients with schizophrenia. A random cluster sampling technique was used, and participants were collected from China National Psychiatric Management System (CNPMS). The variables for clozapine use in individuals with schizophrenia who had undergone a two-year follow-up were determined using the generalized estimating equation (GEE). In this study, 742 patients with schizophrenia were invited, and 491 completed the two-year follow-up study. Being married, more years of education, more waist circumference, using mood stabilizer, using anticholinergic, higher ITAQ (Insight and Treatment Attitude Questionnaire) scores were more significantly related to the use of clozapine. Older age of onset, using second-generation antipsychotics (SGAs) except clozapine predicted a lower prevalence of using clozapine. The usage of clozapine was very common in patients with schizophrenia treated by primary care physicians, and was influenced by a variety of factors, including price of drugs, clinical factors, health regulations, and the characteristics of treatment environment. Further examination of the rationale and appropriateness of clozapine in primary care in China is necessary.

[Adsorption Characteristics of Tetracycline by CuFeO2-modified Biochar].

CuFeO2-modified biochars were prepared through co-precipitation and hydrothermal methods, and the composites had high efficiency removal for tetracycline (TC) from water. The CuFeO2-modified biochar with a 2:1 mass ratio of CuFeO2 to BC450 (CuFeO2/BC450=2:1) demonstrated the best adsorption performance. The kinetic process of TC adsorption by CuFeO2/BC450=2:1 was well fitted with the intraparticle diffusion model, suggesting that the adsorption process was controlled by film and pore diffusion. Under the condition of neutral pH and 298 K, the maximum adsorption capacity of the Langmuir model of CuFeO2/BC450=2:1 was 82.8 mg·g-1, which was much greater than that of BC450 (13.7 mg·g-1) and CuFeO2(14.8 mg·g-1). The thermodynamic data suggested that TC sorption onto CuFeO2/BC450=2:1 was a spontaneous and endothermic process. The removal of TC by CuFeO2/BC450=2:1 increased first and then decreased with increasing pH, and the maximum adsorption occurred under the neutral condition. The strong adsorption of TC by CuFeO2/BC450=2:1 could be attributed to better porosity, larger specific surface area, and more active sites (e.g., functional groups and charged surfaces). This work provided an efficient magnetic adsorbent for removing antibiotics.

A simple and accurate method to quantify real-time contraction of vascular smooth muscle cell in vitro.

Vascular smooth muscle cells (VSMCs) constitute the medial layer of the blood vessel wall. Their contractile state regulates blood flow in physiological and pathological conditions. Current methods for assessing the contractility of VSMCs are not amenable to the high-throughput screening of pharmaceutical compounds. This study aimed to develop a method to address this shortcoming in the field. Real-time contraction was visualized in living VSMCs using the exogenous expression of green fluorescent protein (GFP). Image-Pro Plus software (IPPS) was used to measure various morphological cell indices. In phenylephrine-treated VSMCs, GFP fluorescence imaging was more accurate than brightfield imaging or phalloidin staining in representing VSMC morphology, as measured using IPPS. Among the multiple indices of VSMC shape, area and mean-diameter were more sensitive than length in reflecting the morphological changes in VSMC. We developed a new index, compound length, by combining the mean-diameter and length to differentiate contracted and uncontracted VSMCs. Based on the compound length, we further generated a contraction index to define a single-VSMC contractile status as single-VSMC contraction-index (SVCI). Finally, compound length and SVCI were validated to effectively assess cell contraction in VSMCs challenged with U46619 and KCl. In conclusion, GFP-based indices of compound length and SVCI can accurately quantify the real-time contraction of VSMCs. In future, the new method will be applied to high-throughput drug screening or basic cardiovascular research.

Association of Caffeine Consumption and Brain Amyloid Positivity in Cognitively Normal Older Adults.

BACKGROUND: Several epidemiological studies have reported the protective role of caffeine on health outcomes; however, it remained debatable on caffeine consumption and brain amyloid positivity. OBJECTIVE: We aimed to determine the relationship between caffeine consumption and brain amyloid pathology in cognitively normal older adults. METHODS: The dataset used for analysis in this cross-sectional study was selected from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) Study. Multivariable logistic regression analyses were performed to explore the association between caffeine consumption and amyloid positivity using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In total, 4,394 participants were included in the final analysis. No significant association between caffeine consumption and amyloid positivity was observed in the whole participants (OR, 0.95; 95% CI, 0.78-1.14; p = 0.558). Subgroup analysis showed that caffeine intake was significantly associated with decreased amyloid positivity in males (OR, 0.72; 95% CI, 0.54-0.97; p = 0.032) but not in females (OR, 1.14; 95% CI, 0.90-1.46; p = 0.280), and the association between caffeine and amyloid positivity was not affected by age or APOE genotypes. In addition, different levels of caffeine were not associated with amyloid positivity. CONCLUSION: The findings suggest that caffeine consumption was not significantly associated with amyloid positivity in the whole sample. However, caffeine consumption may be inversely associated with amyloid positivity among males but not females. More studies are needed to explore the mechanisms underlying caffeine consumption and brain amyloid positivity.

Accessibility to Digital Mental Health Services among the General Public throughout COVID-19: Trajectories, Influencing Factors and Association with Long-Term Mental Health Symptoms.

Digital mental health services (DMHSs) have great potential for mitigating the mental health burden related to COVID-19, but public accessibility (ease of acquiring services when needed) to DMHSs during the pandemic is largely unknown. Accessibility to DMHSs was tracked longitudinally among a nationwide sample of 18,804 adults in China from before to one year after COVID-19 outbreak. Unconditional and conditional latent growth curve models and latent growth mixture models were fitted to explore the overall growth trend, influencing factors, and latent trajectory classes of accessibility to DMHSs throughout COVID-19. Generalized estimating equation models and generalized linear mixed models were employed to explore the association between accessibility to DMHSs and long-term mental health symptoms. We found that people generally reported increased difficulty in accessing DMHSs from before to one year after COVID-19 outbreak. Males, youngsters, individuals with low socioeconomic status, and individuals greatly affected by COVID-19 reported greater difficulty in accessing DMHSs. Four DMHS accessibility trajectory classes were identified: "lowest-great increase" (6.3%), "moderate low-slight increase" (44.4%), "moderate high-slight decrease" (18.1%) and "highest-great decrease" (31.2%). Trajectory classes reporting greater difficulty in accessing DMHSs were at higher risk for long-term mental symptoms. In conclusion, an overall increase in difficulty in accessing DMHSs is observed throughout COVID-19, and heterogeneity exists in DMHS accessibility trajectories. Our results suggest that easy access to DMHSs should be consistently facilitated. Moreover, access gaps should be reduced across demographic groups, and target populations for service allocation should alter as the pandemic evolves.

Quality of life in patients with schizophrenia: A 2-year cohort study in primary mental health care in rural China.

Objective: Quality of life (QoL) has been always an important way to evaluate the outcomes of schizophrenia, but there have been few previous longitudinal studies and few in middle-income countries. This study aimed to explore the QoL in Chinese patients with schizophrenia treated in primary mental health care and the risk factors of QoL over time. Methods: Patients with schizophrenia treated in primary mental health care in rural/regional areas in Luoding, Guangdong, PR China, were evaluated with an extended questionnaire including the Chinese version of the World Health Organization Quality of Life (WHOQOL-BREF) at baseline and 2-year follow-up. Bivariate and multivariate analyses were conducted including Generalized Estimated Equation analyses (GEE). Results: Four hundred and ninety-one patients with schizophrenia in primary care completed the 2-year follow up evaluation. The QoL physical, environmental, and social relationships domains showed improvement after the 2-year period, but the psychological domain did not. GEE results showed that earlier age of onset, older age, being employed, being unmarried, the thicker waist circumference, less use of clozapine or other SGAs, fewer hospitalizations, more frequent insomnia, more severe depressive and negative symptoms as well as worse treatment insight were independently associated with poor QoL in patients with schizophrenia. Conclusion: According to our results, to improve the quality of life of patients with schizophrenia in primary care, we should pay more attention to the treatment of depression, negative and insomnia symptoms of schizophrenia, the choice and dosage of antipsychotic medication and improvement in the treatment compliance. The combined use of educational and behavioral strategies may improve treatment adherence.

Long-term psychological profile of general population following COVID-19 outbreak: symptom trajectories and evolution of psychopathological network.

AIMS: COVID-19 has long-term impacts on public mental health, while few research studies incorporate multidimensional methods to thoroughly characterise the psychological profile of general population and little detailed guidance exists for mental health management during the pandemic. This research aims to capture long-term psychological profile of general population following COVID-19 by integrating trajectory modelling approaches, latent trajectory pattern identification and network analyses. METHODS: Longitudinal data were collected from a nationwide sample of 18 804 adults in 12 months after COVID-19 outbreak in China. Patient Health Questionnaire-9, Generalised Anxiety Disorder-7 and Insomnia Severity Index were used to measure depression, anxiety and insomnia, respectively. The unconditional and conditional latent growth curve models were fitted to investigate trajectories and long-term predictors for psychological symptoms. We employed latent growth mixture model to identify the major psychological symptom trajectory patterns, and ran sparse Gaussian graphical models with graphical lasso to explore the evolution of psychopathological network. RESULTS: At 12 months after COVID-19 outbreak, psychological symptoms generally alleviated, and five psychological symptom trajectories with different demographics were identified: normal stable (63.4%), mild stable (15.3%), mild-increase to decrease (11.7%), mild-decrease to increase (4.0%) and moderate/severe stable (5.5%). The finding indicated that there were still about 5% individuals showing consistently severe distress and approximately 16% following fluctuating psychological trajectories, who should be continuously monitored. For individuals with persistently severe trajectories and those with fluctuating trajectories, central or bridge symptoms in the network were mainly 'motor abnormality' and 'sad mood', respectively. Compared with initial peak and late COVID-19 phase, aftermath of initial peak might be a psychologically vulnerable period with highest network connectivity. The central and bridge symptoms for aftermath of initial peak ('appetite change' and 'trouble of relaxing') were totally different from those at other pandemic phases ('sad mood'). CONCLUSIONS: This research identified the overall growing trend, long-term predictors, trajectory classes and evolutionary pattern of psychopathological network of psychological symptoms in 12 months after COVID-19 outbreak. It provides a multidimensional long-term psychological profile of the general population after COVID-19 outbreak, and accentuates the essentiality of continuous psychological monitoring, as well as population- and time-specific psychological management after COVID-19. We believe our findings can offer reference for long-term psychological management after pandemics.

Risk factors for violent behaviors in patients with schizophrenia: 2-year follow-up study in primary mental health care in China.

Objective: The consequences and impact of violent behavior in schizophrenia are often serious, and identification of risk factors is of great importance to achieve early identification and effective management. Methods: This follow-up study sampled adult patients with schizophrenia in primary mental health care in a rural area of southern China, in which 491 participants completed a comprehensive questionnaire at baseline and the 2-year follow-up. Sociodemographic, clinical and psychological assessment data were collected from all participants. Paired sample T-Tests and the McNemar Test were performed to examine changes over the follow-up period. Generalized Estimating Equations (GEE) were used to analyze the risk factors for violent behavior. Results: The results showed that about two in five community-dwelling patients with schizophrenia reported violent behavior in the past year. At follow-up, participants were significantly less employed, had more times of hospitalization, more psychotropic medication, and severer depressive symptoms, but had better health-related quality of life than at baseline. Use of clozapine and better insight into medication decreased the possibility of violent behavior, while more severe positive symptoms, insomnia, as well as use of second-generation antipsychotics other than clozapine, antidepressants and mood stabilizers increased the possibility of violent behavior. Conclusions: Risk evaluation, prevention and management of violence in patients with schizophrenia are demanded in primary mental health care.

Linking knowledge with attitude: a cross-sectional study of public knowledge and attitude towards sleep disturbances and dementia.

OBJECTIVES: Sleep disturbances increase the risk of dementia; however, there is insufficient information regarding this. We aimed to investigate public knowledge on the relationship between sleep disturbances and dementia, as well as attitudes towards improving sleep quality and obtaining knowledge on dementia. DESIGN AND SETTING: A cross-sectional web-based questionnaire was administered between May and October 2019. PARTICIPANTS: All participants provided informed consent and were able to respond to the survey. PRIMARY OUTCOMES: Factors associated with the knowledge that sleep disturbances are risk factors for dementia and proportions of individuals with this knowledge; attitudes towards improving sleep quality and obtaining knowledge about dementia. RESULTS: Of the 3329 eligible samples, 72.57% correctly recognised that sleep disturbances increased the risk of dementia. In total, 92.97% of participants were willing to take at least one measure to improve sleep quality, and the percentages of those adopting these measures are as follows: 78.73% would lead a regular life, 67.88% would engage in strengthening exercise, 28.84% would undergo psychotherapy and 19.41% would take medication. The awareness regarding sleep disturbances increasing the risk of dementia was the only factor associated with the willingness to improve sleep quality in all four categories of measures. Almost all participants (95.25%) were willing to take at least one measure to acquire knowledge about dementia, with the following participants displaying higher willingness to obtain knowledge about dementia: female, had contact with dementia and considered sleep disturbances to increase the risk of dementia. CONCLUSIONS: Our findings indicate an association between people's knowledge and attitudes, suggesting the importance of disseminating knowledge about sleep disturbances and dementia to achieve dementia prevention in future.

Acidic pH irreversibly activates the signaling enzyme SARM1.

SARM1, an executioner in axon degeneration, is an autoinhibitory NAD-consuming enzyme, composed of multiple domains. NMN and its analogs, CZ-48 and VMN, are the only known activators, which can release the inhibitory ARM domain from the enzymatic TIR domain. Here, we document that acid can also activate SARM1, even more efficiently than NMN, possibly via the protonation of the negative residues. Systematic mutagenesis revealed that a single mutation, E689Q in TIR, led to the constitutive activation of SARM1. It forms a salt bridge with R216 in the neighboring ARM, maintaining the autoinhibitory structure. Using this 'acid activation' protocol, mutation K597E was found to inhibit activation, while H685A eliminated SARM1 catalytic activity, revealing two distinct inhibitory mechanisms. The protocol has also been applied to differentiate two classes of chemical inhibitors. NAD, dHNN, disulfiram, CHAPS, and TRX-100 mainly inhibited the activation process, while nicotinamide and Tweens mainly inhibited SARM1 catalysis. Taken together, we demonstrate a new mechanism for SARM1 activation and decipher two distinct inhibitory mechanisms of SARM1.

Excessive expression of miR-1a by statin causes skeletal injury through targeting mitogen-activated protein kinase kinase kinase 1.

BACKGROUNDS: A major side effect of statin, a widely used drug to treat hyperlipidemia, is skeletal myopathy through cell apoptosis. The aim of this study is to investigate the roles of microRNA in statin-induced injury. METHODS: Apolipoprotein E knockout (ApoE-/-) mice were administered with simvastatin (20 mg/kg/day) for 8 weeks. Exercise capacity was evaluated by hanging grid test, forelimb grip strength, and running tolerance test. RESULTS: In cultured skeletal muscle cells, statin increased the levels of miR-1a but decreased the levels of mitogen-activated protein kinase kinase kinase 1 (MAP3K1) in a time or dose dependent manner. Both computational target-scan analysis and luciferase gene reporter assay indicated that MAP3K1 is the target gene of miR-1a. Statin induced cell apoptosis of skeletal muscle cells, but abolished by downregulating of miR-1a or upregulation of MAP3K1. Further, the effects of miR-1a inhibition on statin-induced cell apoptosis were ablated by MAP3K1 siRNA. In ApoE-/- mice, statin induced cell apoptosis of skeletal muscle cells and decreased exercise capacity in mice infected with vector, but not in mice with lentivirus-mediated miR-1a gene silence. CONCLUSION: Statin causes skeletal injury through induction of miR-1a excessive expression to decrease MAP3K1 gene expression.